Expression of the phosphoprotein P53 and also several of the protooncogenes were studied in various differentiating systems. ln the embryonal differentiation of the chicken the decrease in p53 protein was found to be caused by the decrease in the steady state level of the mRNA regulated by a post-transcriptional mechanism. In the differentiation of rabbit epithelial cells induced by edded TGF8 or retinoic acid, or elternately by deprivation of EGF, very large changes in p53 mRNA and also in c-fos and H-ras mRNA were observed, with concomitant well defined changes in cell phenotypes resulting in secretory or in keratinoid cells. Studies on induced embryonal differentiation of carcinoma cells further supported the finding that a decline in p53 mRNA (through a post-transcriptional mechanism) is a general correlate in cellular differentiation. This finding is important, as together with the finding of the conservation of the p53 gene during evolution of the vertebrates from fish through avian to mammalian species, suggests an essential function for p53. P53 cDNA clones were obtained from 3T12 Balb/c mouse cells in which the p53 is unable to complex with the SV40 T antigen. Sequencing and transfection assays are now being carried out to assess if naturally occurring structural changes in the p53 (detectable also by specific monoclonal antibodies) cause the inability for complexing.